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- Title
Impaired neutral sphingomyelinase activation and cutaneous barrier repair in FAN-deficient mice.
- Authors
Kreder, D; Krut, O; Adam-Klages, S; Wiegmann, K; Scherer, G; Plitz, T; Jensen, J M; Proksch, E; Steinmann, J; Pfeffer, K; Krönke, M
- Abstract
The WD-40 repeat protein FAN binds to a distinct domain of the p55 receptor for tumor necrosis factor (TNF) and signals the activation of neutral sphingomyelinase (N-SMase). To analyze the physiological role of FAN in vivo, we generated FAN-deficient mice by targeted gene disruption. Mice lacking a functional FAN protein do not show any overt phenotypic abnormalities; in particular, the architecture and cellular composition of lymphoid organs appeared to be unaltered. An essential role of FAN in the TNF-induced activation of N-SMase was demonstrated using thymocytes from FAN knockout mice. Activation of extracellular signal-regulated kinases in response to TNF treatment, however, was not impaired by the absence of the FAN protein. FAN-deficient mice show delayed kinetics of recovery after cutaneous barrier disruption suggesting a physiological role of FAN in epidermal barrier repair. Although FAN exhibits striking structural homologies with the CHS/Beige proteins, FAN-deficient mice did not reproduce the phenotype of beige mice.
- Publication
The EMBO journal, 1999, Vol 18, Issue 9, p2472
- ISSN
0261-4189
- Publication type
Journal Article
- DOI
10.1093/emboj/18.9.2472